The purpose of this work is to develop a method of "intracellular vaccination" to protect against infection by HTLV-I and HIV. The herpes thymidine kinase (HSV-TK) gene is placed under the regulatory control of the respective long terminal repeats from HIV and HTLV-I. This hybrid gene construct is placed within a replication-defective retroviral vector, which also contains the selectable marker for neomycin resistance. Stably-transformed cell lines containing these TK-containing constructs are made which will produce HSV-TK enzyme in response to wild-type viral infection by HIV or HTLV-I. The sensitivity and lethal response of these engineered cell lines are studied by infecting with wild-type virus and treating with the HSV-TK-specific drug, gangcyclovir. Following successful in vitro experiments, in vivo experiments using SCID mice will be undertaken.